Changes in toxic and antitumor properties of ftorafur by induction or inhibition of the microsomal enzymes activity.
The inducers of microsomal drug-metabolizing enzymes phenobarbital (PB) and 20-methylcholanthrene (MC) inhibited the lethargic effect of high doses of ftorafur in C57BL/6j mice, but stimulated the animal mortality at days 4-8 after the drug administration. The opposite effect has been obtained by the combination of ftorafur with the inhibitor of the microsomal enzymes SKF 525A. Animal pretreatment with PB or with PB + MC markedly enhanced the antineoplastic activity of ftorafur in Rauscher leukemia-, leukemia La-, or hemangiopericytoma-bearing mice but seemed unlikely to afford any therapeutic advantage over this drug because the lethal toxicity of ftorafur was increased.
D000818:Animals; D000970:Antineoplastic Agents; D004347:Drug Interactions; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives*; D008748:Methylcholanthrene / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D008862:Microsomes, Liver / Q000201:enzymology*; D010634:Phenobarbital / Q000494:pharmacology; D005641:Tegafur / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D005641:Tegafur; D008748:Methylcholanthrene; D005472:Fluorouracil; D010634:Phenobarbital